淀粉样β肽（1-42）诱导的阿尔茨海默病氧化应激：在疾病发病机制和进展中的重要性。
Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression.
机构信息
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA.
出版信息
Antioxid Redox Signal. 2013 Sep 10;19(8):823-35. doi: 10.1089/ars.2012.5027. Epub 2013 Feb 14.
Abstract
SIGNIFICANCE
Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (Aβ) that is derived from the proteolytic cleavage of amyloid precursor protein.
RECENT ADVANCES
Recent studies are consistent with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD.
CRITICAL ISSUES
The exact relationships of the specifically oxidatively modified proteins in AD pathogenesis require additional investigation.
FUTURE DIRECTIONS
Further studies are needed to address whether the therapies directed toward brain oxidative stress and oxidatively modified key brain proteins might help delay or prevent the progression of AD.
摘要
意义
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病。AD 的特征是进行性认知障碍。AD 大脑的主要组织病理学特征之一是存在老年斑（SPs），另一个是氧化应激升高。SP 的主要成分是淀粉样β肽（Aβ），它来源于淀粉样前体蛋白的蛋白水解裂解。
最新进展
最近的研究与以下观点一致，即 Aβ 中 35 位的蛋氨酸对 Aβ 诱导的氧化应激和神经毒性至关重要。此外，我们还讨论了在 AD 进展过程中，使用氧化蛋白质组学方法鉴定的氧化修饰脑蛋白的特征。
关键问题
AD 发病机制中特定氧化修饰蛋白的确切关系需要进一步研究。
未来方向
需要进一步研究，以确定针对大脑氧化应激和氧化修饰关键脑蛋白的治疗方法是否有助于延缓或预防 AD 的进展。
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